title: The rno-miR-34 family is upregulated and targets ACSL1 in dimethylnitrosamine-induced hepatic fibrosis in rats.
abstract: The mechanisms whereby hepatic fibrosis develops in chronic liver diseases remain incompletely defined. Here, we sought to examine whether microRNA (miRNA) became dysregulated in dimethylnitrosamine-induced hepatic fibrosis in rats. Our microarray analysis revealed that the miR-34 family was upregulated along with other miRNAs in liver fibrotic tissues. Six miRNAs, such as rno-miR-878, were downregulated. The findings were confirmed by RT-PCR assays. Gene ontology analysis further showed that many of these dysregulated miRNAs were involved in lipid/fatty acid metabolism. The acyl-CoA synthetase long-chain family member 1 (ACSL1) gene contained specific binding sites for miR-34a/miR-34c. Additional enhanced green fluorescence protein reporter activity assays indicated that the miR-34 family targeted ACSL1. Our RT-PCR and immunoblotting assays further demonstrated that both the mRNA and protein levels of ACSL1 were markedly reduced in fibrotic liver tissues. Our findings suggest that miRNA becomes dysregulated during hepatic fibrosis, and that the miR-34 family may be involved in the process by targeting ACSL1.
authors.affiliation: Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wei-Qing
authors.initials: WQ
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Mi-Die
authors.initials: MD
authors.lastname: Xu
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Li
authors.forename: Qing-Mei
authors.initials: QM
authors.lastname: Xia
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Liu
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Yu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000818:Animals; D003066:Coenzyme A Ligases / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D003066:Coenzyme A Ligases; C561832:Acsl1 protein, rat; D004128:Dimethylnitrosamine